Deregulated TCR alpha beta T cell population provokes extramedullary hematopoiesis in mice deficient in the common gamma chain

被引:30
作者
Sharara, LI [1 ]
Andersson, A [1 ]
Fischer, A [1 ]
DiSanto, JP [1 ]
机构
[1] HOP NECKER ENFANTS MALAD,INSERM,U429,F-75743 PARIS,FRANCE
关键词
cytokine receptor; immunodeficiency; extramedullary hematopoiesis; lymphoid homeostasis; activated T cell;
D O I
10.1002/eji.1830270428
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Deficiency of the cytokine receptor common gamma chain (gamma(c)) results in abnormal lymphoid development and a severe immunodeficiency disease due to the combined loss of the receptors for interleukins (IL)-2, -4, -7, -9, and -15. We have observed the development of secondary hematopoiesis with circulating hematopoietic progenitor cells in adult mice harboring a null mutation in gamma(c). These extramedullary changes were not secondary to bone marrow failure or to an inability to maintain circulating blood counts. These results suggested that gamma(c)-dependent cytokine signaling pathways modulate hematopoietic development. An intrinsic defect in gamma(c)(-) hematopoietic stem cell committment appeared unlikely, as fetal liver hematopoiesis was unaltered in gamma(c)(-) embryos. Furthermore, the absence of natural killer cells in gamma(c)(-) mice was not responsible for the observed hematopoietic changes. Peripheral TCR alpha beta T cells from gamma(c)(-) mice were characterized by an activated phenotype (CD62L(lo), CDL44(hi), CD69(hi)) and showed increased levels of transcripts for hematopoietic stimulating cytokines, including IL-3 and granulocyte/macrophage-colony stimulating factor. A predominance of these cells was detected in the bone marrow, suggesting a role for residual T cells in the enhanced hematopoiesis. Strikingly, the elimination of residual T cells from gamma(c)(-) mice reduced splenic and circulating hematopoietic precursor frequencies to normal levels. These results clearly implicate a deregulated TCR alpha beta T cell population in the observed hematopoietic changes in gamma(c)(-) mice, and emphasize the importance of gamma(c)-dependent cytokine interactions in modulating mature T cell responses.
引用
收藏
页码:990 / 998
页数:9
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